There is a need for simple, efficacious, and patient-acceptable contraceptive methods. The objective of the research application is to demonstrate in vivo the feasibility of developing such a method which is based on the controlled percutaneous absorption of levonorgestrel contraceptive from a skin patch. The rate of drug release will be controlled by a microcapsule diffusional barrier and a USFDA approved "enhancer" in a dermatologically acceptable viscous liquid base. Topical delivery systems have recently become commercially available. One of the most popular is for the delivery of nitroglycerin to cardiac patients. Three approaches have been used, but they all depend upon a membrane for diffusional control. The membrane does not always make intimate contact with the skin. In our skin patch however, intimate contact is continously maintained with the skin and the rate limiting step is the microcapsule wall and the "enhancer" which is present in the dermatological base. We have prepared levonorgestrel microcapsules which range in size from a few to several hundred microns. The rate of drug release is controlled by varying microcapsule size and wall thickness. Our objective is to evaluate the feasibility of percutaneous absorption of levonorgestrel from a skin patch in vivo using rabbits, and to identify the most important variable which controls the delivery of the steroid to the blood stream. Blood levels of the drug will be monitored by an enzyme immunoassay method we developed. The delivery of contraceptives through a skin patch offers real advantages in terms of user flexibility. The approach presented in this application is one which utilizes USFDA approved drugs and microcapsules which have been developed for the Contraceptive Development Branch. These microcapsules will soon undergo toxicity studies in animals to be followed by clinical studies. This should greatly facilitate and reduce the costs associated with the transition of the patch from the laboratory to the market place.